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Poster display session

3107 - Efficient identification of neoantigens for personalized cancer immunotherapy in advanced refractory epithelial cancer patients

Date

10 Sep 2017

Session

Poster display session

Presenters

Fangjun Chen

Citation

Annals of Oncology (2017) 28 (suppl_5): v403-v427. 10.1093/annonc/mdx376

Authors

F. Chen, Z. Zou, J. Du, J. Wei, J. Shao, F. Meng, N. ding, B. Liu

Author affiliations

  • The Comprehensive Cancer Centre Of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, China, 210008 - Nanjing/CN
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Resources

Abstract 3107

Background

Recent genomic and bioinformatic technological advances have made it possible to dissect the immune response to personalized neoantigens encoded by tumor-specific mutations. However, rapid and efficient identification of neoantigens is still fraught with difficulty, and a systematic evaluation of personalized neoantigens based immunotherapy in advanced refractory epithelial tumors is lacking.

Methods

Tumor and ctDNA samples from 16 advanced epithelial cancer patients were underwent mutational profiling by cancer-associated genes panel. Neoantigens identification were performed by two strategies:(1) As classic mode, somatic mutations were subjected to in silico analysis to predict potential high-affinity epitopes and mutated peptides were denovo synthesized; (2) Hotspot mutations were matched to our customized driver mutation-derived neoantigens peptide library. Candidate neoepitopes were identified. Approximately 108 neoantigen loaded DC vaccine and 1010 bulk T cells composed of 109 neoantigen reactive CD8+T cells were generated for personlized immunotherapy.

Results

Among the sequenced patients, 1∼2 neoantigens recognized by autologous T cells have been successfully identified in 3 of 4 patients who utilized the classic mode and 6 of 12 patients who performed customized neoantigens library, respectively. Subsequently, a total number of 6 patients received immunotherapy targeting personalized neoantigen following immunomodulatory chemotherapy or radiotherapy. One patient with metastatic thymoma is achieving a complete and durable response beyond 12 months. In addition, immune related partial response was observed in another advanced pancreatic cancer patient. The remaining 4 patients achieved prolonged stabilization of disease with median PFS of 8.6 months.

Conclusions

Our costomized neoantigens library can provide a novel approach for neoantigens screening in advanced epithelial cancer patients. Besides, targeted sequencing is sufficient for somatic variant and neoantigen identification. The combination of two strategies can accelerate the neoantigen-based translational immunotherapy research into the paradigm of precision medicine.

Clinical trial identification

Legal entity responsible for the study

Baorui Liu

Funding

None

Disclosure

All authors have declared no conflicts of interest.

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